The objective of this project is to biochemically and physically define the enzyme branched chain alpha-ketoacid dehydrogenase. The enzyme has been solubilized and partially purified from rat and beef liver. It will oxidatively decarboxylate only alpha-ketoisovalerate, alpha-ketoisocapirate and alpha-keto-beta-methylvalerate preferentially in this order. A genetic disorder inherited as an autosomal recessive trait specifically affects the function of this enzyme. The defect is expressed in skin fibroblasts cultured from affected individuals. By coordinating the studies on the purified enzyme with those using cultured cells to study the genetic defect, we are continuing to improve the in vivo management of humans affected with Maple Syrup Urine Disease. Diet therapy and vitamin B1 supplementation has already aided in the prevention of disabling mental and physical retardation resulting from this genetic abnormality in selected individuals. Through continued study better rationale can be developed for more improved management of all patients affected with this abnormality. BIBLIOGRAPHIC REFERENCES: Elsas, L.J., Danner, and Rogers, B.A. Effect of Thiamine on Normal and Mutant Human Branched Chain alpha-ketoacid Dehydrogenase. Thiamine. Ed. by C. Gubler, M. Fujiwara, P. Dreyfus, Wiley Interscience, New York (1976) p. 335-352. Marion, J.P., Danner, D.J., Ballou, W.R., Marion R. and Elsas, L.J. Southern Medical Journal. Testing for the Tay Sachs Gene in the Atlanta Jewish Population, 1977, in press.